Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/180519
Title: | A New Pipeline for the Normalization and Pooling of Metabolomics Data |
Author: | Viallon, Vivian His, Mathilde Rinaldi, Sabina Breeur, Marie Gicquiau, Audrey Hemon, Bertrand Overvad, Kim Tjønneland, Anne Rostgaard-Hansen, Agnetha Linn Rothwell, Joseph A. Lecuyer, Lucie Severi, Gianluca Kaaks, Rudolf Johnson, Theron Schulze, Matthias B. Palli, Domenico Agnoli, Claudia Panico, Salvatore Tumino, Rosario Ricceri, Fulvio Verschuren, W. M. Monique Engelfriet, Peter Onland-Moret, N. Charlotte Vermeulen, Roel Nøst, Therese Haugdahl Urbarova, Ilona Zamora-Ros, Raul Rodriguez Barranco, Miguel Amiano, Pilar Huerta, José María Ardanaz, Eva Melander, Olle Ottoson, Filip Vidman, Linda Rentoft, Matilda Schmidt, Julie A. Travis, Ruth C. Weiderpass, Elisabete Johansson, Mattias Dossus, Laure Jenab, Mazda Gunter, Marc J. Lorenzo Bermejo, Justo Scherer, Dominique Salek, Reza M. Keski-Rahkonen, Pekka Ferrari, Pietro |
Keywords: | Metabolòmica Càncer Metabolites Cancer |
Issue Date: | 17-Sep-2021 |
Publisher: | MDPI AG |
Abstract: | Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis; (iii) application of linear mixed models to remove unwanted variability, including samples' originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/metabo11090631 |
It is part of: | Metabolites, 2021, vol. 11, num. 9, p. 631 |
URI: | https://hdl.handle.net/2445/180519 |
Related resource: | https://doi.org/10.3390/metabo11090631 |
ISSN: | 2218-1989 |
Appears in Collections: | Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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metabolites-11-00631.pdf | 3.13 MB | Adobe PDF | View/Open |
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